Dystonia is a disabling neurological disorder characterized by involuntary twisting movements and postures. Dystonia may be idiopathic or secondary to known environmental or metabolic factors. No marker, pathological or biochemical, has been identified in idiopathic dystonia. However based on clinical and ethnic criteria and familial patterns, subtypes have been described and genetic heterogeneity proposed. Included in these subtypes are (1) Ashkenazi Jews, (2) non- Jewish caucasians and (3) non-Ashkenazi caucasians with dopa responsiveness. Because of our rich resource of patients, clinical expertise, and team of experienced geneticists, we are in a unique position to locate and ultimately identify the defective gene(s) underlying idiopathic dystonia and establish whether the same locus is involved in each group through linkage heterogeneity test. We propose to perform linkage studies on families that are representative of the three subtypes of dystonia described above. Detailed and unbiased clinical assessment of informative large and small families will be performed. Blood samples from informative family members will be collected for DNA and protein marker determination. We will search for a linked marker within individual large families ethnic subtype. We will test for genetic heterogeneity both within and between subgroups. Once a linked marker to one or more disease subtypes is found, we will define further the genomic region containing the dystonia gene with the ultimate aim of identification of the defective gene. The results of this study are directly applicable in the clinical setting. Finding a closely linked marker will allow for reliable risk assessment in counseling of families. Further identification of the mutant gene will ultimately elucidate the mechanism(s) underlying this mysterious disorder and could provide a basis for specific treatment.